Genomic Variation & Disease / RNA & Transcriptomics

what is personalised medicine

a medical model that proposes to customize medical decisions, practices, and treatments for the individual patients

what is the aim of personalised medicine

to select appropriate therapies for the individual patient to ensure the best possible outcome and reduce the risk of side effects

what is a biomarker

something that can be measured and points to the presence of:

• a disease

• a physiological change

• a response to treatment

• psychological condition

what is gene therapy

process by which a sequence of DNA/RNA is introduced to the cells which results on the formation of a protein which is needed for recovery

what is gene editing

the process by which genetic tools are used to delete or insert sections of DNA to prevent disease/introduce new function

• CRISPR-CAS9

• endonucleases

what is artificial cell therapy

• design a cell programmed to make a native protein from a wildtype gene

• deliver cell to parts of the body that require the protein for function

what is protein replacement therapy

process of providing individuals with a supply of functional proteins which may be dysfunction/absent in their body

what are some general struggles with personalised medicine treatments

• delivery of treatment to target cells

• uptake of treatment by target cells

• cost

• does this approach actually help the patient

• time & cost of creating the drug/protein/cell

• early stages of development/needs more research

how is DNA packaged

packaged in nucleosomes, which condense to form chromatin fibres

• these are packaged as chromosomes

what are lamina associated domains (LADs)

parts of the chromosome that are associated with the nuclear lamina, they are areas of lower gene expression

• lamina is an inner layer of the nucleus responsible for structural integrity & gene regulation

how are LADs formed

via interactions between DNA & anchors in nuclear lamin

• some LADs are constitutive (cLADs) or facultative (fLADs)

• LADs are dynamic and change during mitosis & cell development

what is important to note about the structure of genes

they are looped, this allows promoters that are a downstream to interact with upstream components

what are TADs

topologically-associating domains

• structural units that describe how DNA is folded in the nucleus

what is CTCF

a zinc finger protein that binds to DNA and demarcates the TAD boundaries

what is cohesion

a circular multi-protein complex that acts as a collar to form the TAD

how are TADs identified with Hi-C

what is epigenetics

refers to the alteration of histones to regulate gene expression

• methylation, phosphorylation, ubiquitarian, acetylation

how does H3K27 turn off transcription

requires an enzyme EZH2 which functions in a complex called PRC2

• complex adds 3 methyl groups onto K27 which ultimately results in deactivating transcription